20 December 2012

2012 Review of the year

Highlights of the Institute's research and activities over the past year

In 2012, our genomic techniques and resources yielded insights and knowledge that will impact healthcare and biological research for years to come.

Our mission is to undertake the basic science that informs and accelerates the incorporation of genome science into medical research. This year our researchers have delved deeper into our genetic history to understand what makes us human, laid firm foundations for biological researchers around the world and are changing medical practice.

Genomes changing medical practice

C. difficile

C. difficile [Genome Research Limited]


In November 2012, for first time, our researchers announced that they had used real-time genome sequencing to help stop an MRSA outbreak at a UK NHS Hospital. The team were working with Addenbrooke's Hospital, Cambridge to test whether or not DNA sequencing could rapidly and accurately map the spread of the bacteria through the hospital by looking at an old outbreak, when the outbreak started up again. They identified that the new outbreak was closely related to the original infection and helped the hospital to rapidly identify unwitting MRSA carrier, remove the bacteria and bring the infection to a halt. This is a dramatic demonstration that medical genomics is no longer a technology of the future - it is a technology of the here and now.

To improve cancer treatment, our researchers are conducting the world's largest study of the effect of genetic changes on anti-cancer drug sensitivity: the Genomics of Drug Sensitivity in Cancer Project. In March they published the responses of 600 cancer cell lines to 130 drugs, revealing new treatment options and targets for development. Among their findings they discovered a new, gentler treatment option for Ewing's sarcoma an aggressive bone cancer in children and young adults. Further research is now needed to see if the drug, which is currently used to treat breast and ovarian cancers, is effective in patients.

Painstaking genome sequencing also ended a 50-year hunt for the cause of a rare skeletal and blood disorder: the genetic basis of Thrombocytopenia with Absent Radii (TAR) syndrome. This work will now allow an antenatal diagnostic test to be developed and will enable improved genetic counselling for at-risk families. Our work to improve understanding of human health and disease extends beyond working with human cells and draws on our expertise in working with mice and sequencing pathogens. For example, combining these two skills enabled our research teams to develop a novel treatment for C. difficile infections in mice, which are responsible for 2,000 deaths in the UK each year.

Certain strains of C. difficile infection are highly contagious and become the predominant bacteria in a person's gut. Treating the bacteria with antibiotics can be in-effective and the surviving bacteria then multiply and take over the gut again. It is known that 'seeding' the gut with healthy bacteria by using fecal therapy can stop C. difficile from becoming re-estabished. However, faecal matter is unlikely to adopted as a mainstream treatment, so our researchers have used mice models and pathogen sequencing to isolate and identify a cocktail of naturally occurring bacteria that will prevent C. difficile establishing in the guts of in mice, opening new doors for a new treatment in humans.

Unravelling cancer's complex secrets

In May, our Cancer Genome Project published two landmark studies on how breast cancer develops. They showed that mutations in the cells accumulate slowly over a number years, picking up more momentum as the genetic damage builds. They also identified novel processes responsible for mutation: one, called kataegis (Greek for thunderstorm), was present in the genome of 13 of the 21 breast cancers and produces massive levels of mutation in small regions of the genome. This knowledge of the landscape of cancer mutation and development will help to inform future research into targets for improved diagnosis and treatment - by isolating the root changes at the heart of cancer formation.

Exploring our human condition


Kamilah. [San Diego Zoo]


New discoveries in genetics are changing our understanding of ourselves and the natural world. In March the Institute published the complete genome of the gorilla, the last of the great apes to be sequenced. For the first time we are now able to compare the genomes of all four living great apes: humans, chimpanzees, gorillas and orang-utans. This study provided a unique perspective on our own origins and is an important resource for research into human evolution and biology, as well as for gorilla biology and conservation. For example, we now know that the development of human language is unlikely to be due to the development of our hearing genes: gorillas show similar genetic evolution but don't have complex language.

In June our researchers peered into our genetic roots and uncovered a tantalising link to the famous story of the Queen of Sheba bearing a son from the Israelite King Solomon. Our scientists investigated the genetic heritage of Ethiopian populations, who are among the most diverse in the world and lie at the gateway from Africa. They discovered that the genomes of some Ethiopian populations bear striking similarities to those of populations in Israel and Syria. The team detected mixing between some Ethiopians and non-African populations dating to around 3000 years ago - approximately the time the Queen is said to have visited Israel to ask her hard questions.

On a darker note, in March our researchers discovered that your genetic makeup has a direct influence on your ability to survive a viral infection. By working together with many collaborators to study the 2009 influenza pandemic, Institute scientists showed that genetic variants in the IFITM3 gene alter a person’s ability to fight off H1N1 influenza virus. This finding may inform future health prevention strategies and allow new therapies to be developed.

Another of our teams is exploring the bond that forms between mother and child. One of our mice teams has investigated roots of baby mice's automatic behaviour to find and suckle from their mother's breast. Until now the prevailing thought has been that pheromones - chemicals that trigger an innate behaviour – drove the suckling response. But our researchers have shown that, in mice, suckling is actually a learned response built on learning the mother's unique combination of smells. Because humans also form an intensive, nurturing bond with their babies, much like mice, this suggests that genetic manipulation of the ability to smell in mice will be a useful way to research the neural pathways involved in human instinctive behaviour.

Laying firm foundations for future research

A decade on from the human genome project, the ENCODE Project released an encyclopaedia of the human genome in September. This is the first detailed map of human biology - a Google Earth of biomedical research - that allows us to zoom in to the smallest detail on the genome and see how that area works and interacts with other genome elements.

Within the gargantuan effort of ENCODE, our researchers led the GENCODE Consortium to deliver accurate gene descriptions for more than 10,000 novel genes, data that are delivered through genome databases around the world. This baseline for biology reveals that the genome is far more active than we originally thought and is opening up new areas of understanding of both common and rare diseases.

With the power of new technologies to conduct large-scale analyses of across hundreds of genomes, we have identified the genetic regions and pathways that underlie both rare and common diseases. Using a DNA chip that can identify more than 200,000 genetic variations in areas associated with metabolic disease, our researchers found 38 new genetic regions that are associated with glucose and insulin levels in the blood. The chip - known as Metabochip - is a more cost-effective and 100-fold more powerful method to find and map genomic regions for a range of cardiovascular and metabolic characteristics on a large scale.

Similar work with Immunochip - a DNA chip designed to find genetic variants involved in the immune system - identified three genetic regions associated with primary biliary cirrhosis (PBC). These findings increase the number of known regions associated the most common autoimmune liver disease to 25.

Crossing continents

Applying our sequencing methods and pathogens expertise has allowed us to show that the emergence and spread of a rapidly evolving invasive intestinal disease might have been facilitated by the HIV epidemic in Africa. Invasive non-Typhoidal Salmonella disease emerged from two hubs in Africa 52 and 35 years ago, has acquired resistance to several front-line drugs and can kill 45 per cent of infected people in sub-Saharan Africa. This discovery is now driving research to aid health prevention strategies.

Professor Gordon Dougan, who led this study, became the Institute's fifth researcher elected Fellow of the Royal Society, recognising his 'important contributions to basic studies on the molecular basis of the infection process, genomics and to the development of practical vaccines'.

Tasmanian devil.

Tasmanian devil. [Steve Johnson, Tasmania Parks and Wildlife Service]

In the southern hemisphere the Tasmanian devil is facing extinction from a transmissible facial cancer that has been circulating for 20 years. Our team sequenced genomes from 69 Tasmanian devil tumour samples, cataloguing the mutations that allowed the cancer to arise and spread, and offering clues to how the disease outwits the immune system. For her research into this condition, Elizabeth Murchison was awarded the 2012 Eppendorf Young Scientist Award and along with Nicole Soranzo, was also awarded the MRC Science Heirloom.

Another of our faculty, Professor Karen Steel, was jointly awarded the 2012 Brain Prize for her cutting edge, fundamental research into understanding the molecular, cellular and physiological mechanisms behind deafness. This award highlights the tremendous research being carried out at the Institute by researchers to understand the rudimentary elements of human biology that in the future could be used manage and treat diseases. Karen has now moved to King's College, London and we wish her continuing success with her research.

Our future

Looking to the year ahead, we will focus on investigating a broad spectrum of diseases and opportunities to develop its discoveries into treatments and diagnostic tests while maintaining its focus on discovery and basic science. In addition, as genetic knowledge and discoveries become part of mainstream cultural discourse, we will seek to engage with a wide range of publics, to help develop interest and understanding of the potential and challenges of the fast-moving world of genetic research.

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